In recent years, the prevalence of dengue, a virus transmitted by the Aedes mosquito bite, has soared. With around 100 million new incidences of dengue per year worldwide, the World Health Organization today considers the dengue virus to be endemic in 100 nations, with the American, South-East Asian, and Western Pacific regions among the most severely afflicted1. Pakistan in South-East Asia due to its subtropical position and climate tolerance for vectors, suffers from thousands of cases of morbidity and hundreds of fatalities from complications of this illness, especially during the monsoon season2. The reason that visitors from nonendemic regions traveling to dengue-affected regions also face the risk of contracting the disease has resulted in a massive increase in the number of people at risk making it a widespread global health issue that needs addressing, particularly in tropical nations1. Dengue is a febrile sickness and presents with rash, myalgia, arthralgia, and headache. Thrombocytopenia, defined as a platelet count of <100,000 cells/mm3 is a typical feature of this infection, which on worsening leads to increased permeability of vessels and plasma leakage, a red flag sign citing for dengue hemorrhagic fever (DHF)3. About 500,000 cases of DHF reported around the world annually require hospitalization and, if left unattended, have a fatality rate of 10%–20%3,4. Despite this potentially fatal consequence, there are yet no efficient antiviral synthetic medicines for dengue infection, the most alarming element of the dengue crisis3. The goals of current therapy options are to reduce complication rates and symptom severity. One such essential therapy in the treatment of dengue is fluid therapy. For dengue fever, oral fluid replacement is sufficient; however, intravenous fluid replacement for shock avoidance is necessary in cases of severe dengue5. The US Food and Drug Administration has not yet authorized any particular drugs for treatment against dengue although clinical trials have examined a number of potential antidengue therapeutics (that target the virus or the host), including carbazochrome sodium sulfonate for capillary leakage prevention6, oral prednisolone as an anti-inflammatory agent7, and lovastatin (statin) as an antidengue virus and anti-inflammatory at the endothelium8. Although symptomatic therapy is effective in most mild instances, certain cases quickly deteriorate into complications, making it challenging to save the patient’s life3. Moreover, future fluctuations in climate, travel, socioeconomic position, commerce, and structural features of the viruses are predicted to lead to a rise in the number of annual dengue cases9. These circumstances underline the necessity for the advent of alternative treatments for complications of dengue infection. Moreover, with the recent floods in Pakistan and the consequent surge in dengue10, the possible therapeutic benefit of Carica papaya (C. papaya) leaf juice has been the subject of much interest and controversy alike. The papaya plant has been shown to have an impact on dengue by alleviating thrombocytopenia because of its membrane-stabilizing properties. This is because of the presence of flavonoids and other phenolic chemicals that have repressing actions on the protease involved in viral assembly as speculated by scientists3. These flavonoids have been shown to increase the white blood cell and platelet count either through a possible stimulatory effect on the bone marrow1 or due to increased expression of the arachidonate 12-lipoxygenase (ALOX12) gene. The increase in platelet count is in fact rapid as proved by a study on the website of the British Medical Journal. The platelet counts of 2 dengue-infected infants as demonstrated by dengue antigen in serum recovered quickly. Every 4 hours, the boys, who were 10 and 14 years old, received a teaspoon of paste made from mashed papaya leaves. The number of platelets surged dramatically; in one case, it reached 100,000 within 12 hours after starting treatment. In the second instance, it rose to 250,000 in <2 days3. In addition to this, according to one other study, the papaya plant’s leaves offer an excellent source of a variety of minerals, which might help in balancing the mineral shortage brought on by the virus and fortify the immune system’s defenses against it11. Equally important is the efficiency of the papaya plant against the Aedes mosquito in addition to its action against the virus, so, if demonstrated to be efficient, this plant could reduce dengue load at 2 distinct stages, at the level of transmission as well as the host level3. Without a doubt, papaya extract offers a reasonably priced and perhaps successful dengue cure. As a result of its membrane-stabilizing properties, the chance that a patient would experience plasma leakage as a result of heightened vascular permeability and capillary fragility can be decreased drastically. Also, the average length of hospital stay can be significantly reduced with a decreased risk of various serious complications because of the rapid increase in platelet count. Although papaya leaf extract or other papaya preparations for dengue fever are advocated by traditional medicine practitioners and the common public, doctors are yet to adopt it in clinical practice12. This is because the scientific literature available has not only reported side effects (eg, nausea, vomiting, and rashes)1 but must also be interpreted with caution. For example, an article in the Journal of Medicinal and Aromatic Plants does not confirm the diagnosis nor mention what other supplemental treatment was administered and whether the improvement in platelet count is significant. The changes in platelet count after 24 hours are also not determined. The dose of extract administered was incoherent among the studies. Therefore, the active principle should be determined, and its dose standardized to truly prove its efficacy3. The usefulness of the extract in severe cases of Dengue Fever or DHF could also not be ascertained as they were excluded from the study1. It is also possible that the rise in platelet count, though statistically significant, may be insufficient to have an impact on clinical outcomes9. The form, in which the extract was administered, might also possibly have a bearing on the results13. Furthermore, animal studies have been performed to explore the systemic effects of C. papaya extract. For example, the African catfish Clarias gariepinus showed behavioral changes, loss of reflexes, peeling skin as well as a drop in several hematological parameters, such as packed cells volume, hemoglobin, red blood cell, and mean corpuscular hemoglobin concentration in time and dose-dependent manner. Similarly, male Wister rats experienced a significant reduction in sperm count (P < 0.05)12. Cytotoxic effects were also observed in the bone marrow cells and splenocytes of rats. Further, a significantly lower level of alanine aminotransferase (P < 0.05) was found. While reproductive function in both male and female animals was compromised after the treatment of up to 21 days, the adverse effect of the C. Papaya leaves on the reproductive system in humans, if at all, is yet to be proven clinically13. While C. Papaya holds promise in the fight against dengue, the disparity in results and lack of standardization call for further investigative research. Clinical trials and data analyses are required to help provide a clearer picture. Cost-effective analyses should also be sought to improve public availability and accessibility in nearly all dengue-endemic nations. In light of the above discussion, it is evident that this possible new treatment if implemented, could potentially change the paradigm of clinical management leading to both fewer and shorter hospital stays. Ethical approval This paper did not involve patients; therefore, no ethical approval was required. Sources of funding The authors received no extramural funding for the study. Author contributions A.W.K., T.N.A., U.A.A.M., and A.S.: conceptualization and literature and drafting of the manuscript. A.W.K. and U.A.A.M.: editing and supervision. Conflicts of interest disclosures The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) NA. Guarantor All authors take responsibility for the work, access to data and decision to publish.